title: Defining the earliest step of cardiovascular progenitor specification during embryonic stem cell differentiation.
abstract: During embryonic development and embryonic stem cell (ESC) differentiation, the different cell lineages of the mature heart arise from two types of multipotent cardiovascular progenitors (MCPs), the first and second heart fields. A key question is whether these two MCP populations arise from differentiation of a common progenitor. In this paper, we engineered Mesp1-green fluorescent protein (GFP) ESCs to isolate early MCPs during ESC differentiation. Mesp1-GFP cells are strongly enriched for MCPs, presenting the ability to differentiate into multiple cardiovascular lineages from both heart fields in vitro and in vivo. Transcriptional profiling of Mesp1-GFP cells uncovered cell surface markers expressed by MCPs allowing their prospective isolation. Mesp1 is required for MCP specification and the expression of key cardiovascular transcription factors. Isl1 is expressed in a subset of early Mesp1-expressing cells independently of Mesp1 and acts together with Mesp1 to promote cardiovascular differentiation. Our study identifies the early MCPs residing at the top of the cellular hierarchy of cardiovascular lineages during ESC differentiation.
authors.affiliation: Université Libre de Bruxelles, Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire, B1070 Bruxelles, Belgium.
authors.forename: Antoine
authors.initials: A
authors.lastname: Bondue
authors.forename: Simon
authors.initials: S
authors.lastname: Tännler
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Chiapparo
authors.forename: Samira
authors.initials: S
authors.lastname: Chabab
authors.forename: Mirana
authors.initials: M
authors.lastname: Ramialison
authors.forename: Catherine
authors.initials: C
authors.lastname: Paulissen
authors.forename: Benjamin
authors.initials: B
authors.lastname: Beck
authors.forename: Richard
authors.initials: R
authors.lastname: Harvey
authors.forename: Cédric
authors.initials: C
authors.lastname: Blanpain
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D002454:Cell Differentiation; D019070:Cell Lineage; D053595:Embryonic Stem Cells / Q000166:cytology*; D020869:Gene Expression Profiling; D049452:Green Fluorescent Proteins / Q000032:analysis; D006321:Heart / Q000196:embryology; D018398:Homeodomain Proteins / Q000378:metabolism; D060850:LIM-Homeodomain Proteins; D051379:Mice; D009206:Myocardium / Q000166:cytology*; D011993:Recombinant Fusion Proteins / Q000032:analysis; D014157:Transcription Factors
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D049452:Green Fluorescent Proteins; D018398:Homeodomain Proteins; D060850:LIM-Homeodomain Proteins; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; C101538:Mesp1 protein, mouse; C063843:insulin gene enhancer binding protein Isl-1